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Brain Cancer Drug Aldoxorubicin Shows Promise in Mid-Stage Trial

Treatment helps doxorubicin cross blood–brain barrier

Positive results have been announced from an ongoing phase II trial of aldoxorubicin for the treatment of unresectable glioblastoma multiforme (GBM), a deadly form of brain cancer.

The open-label study was designed to investigate the preliminary efficacy and safety of aldoxorubicin in patients whose tumors have progressed after prior treatment with surgery, radiation, and temozolomide.

Aldoxorubicin combines doxorubicin with a single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thereby increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not in the neutral environment of healthy tissues, doxorubicin is released. This allows larger doses of doxorubicin to be administered while reducing its toxic effects. There has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of the drug in excess of 2,000 mg/m2.

In the ongoing phase II study, preliminary results in 12 patients showed both prolonged stable disease and tumor shrinkage in several patients, including one patient who demonstrated no microscopic evidence of tumor when tissue was examined after resection, representing a complete response. These observations suggest that aldoxorubicin allows doxorubicin to cross the tumor’s blood–brain barrier in humans, according to the drug’s developer (CytRx Corporation).

The trial’s primary objective is to determine progression-free survival at 6 months and overall survival in patients with recurrent GBM. The principal secondary objective is to evaluate the safety of aldoxorubicin, as assessed by the frequency and severity of adverse events. Only patients who have not received prior treatment with bevacizumab (Avastin) are eligible to participate in the trial.

The study is expected to enroll up to 28 patients, who will be randomly assigned to receive either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalent) of aldoxorubicin intravenously on day 1 and every 21 days thereafter until evidence of tumor progression, unacceptable toxicity, or withdrawal of consent. The tumor response is monitored every 6 weeks by magnetic resonance imaging until disease progression occurs.

GBM is the most common and most malignant primary brain tumor in adults, affecting more than 12,000 new patients in the U.S. each year. Despite surgical resection, radiotherapy, and chemotherapy, the median survival after diagnosis is approximately 14 months. The limited efficacy of chemotherapeutic agents has been attributed to several factors, including insufficient delivery to the tumor site through the blood–brain barrier.

Source: CytRx Corporation; January 6, 2015.


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